Iodoethane → ethyl 5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}nicotinate

HRID 2376140Notes

Reaction equation

HRID 2376140 reaction equation
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].I[CH2:13][CH3:14].C(=O)([O-])[O-].[K+].[K+].Cl.Cl.[CH:23]1([CH2:29][N:30]2[CH2:35][CH2:34][CH2:33][C@@H:32]([NH2:36])[CH2:31]2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1>CN(C)C=O.O>[Cl:1][C:2]1[C:3]([NH:36][C@@H:32]2[CH2:33][CH2:34][CH2:35][N:30]([CH2:29][CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)[CH2:31]2)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([O:9][CH2:13][CH3:14])=[O:8]

Participants

7

Reactant 4

HCID 6340IodoethaneHCID 11430Potassium Carbonate2×HCID 2479875,6-Dichloronicotinic acidHCID 68961053(3R)-1-(cyclohexylmethyl)-3-piperidinamine dihydrochloride

Product 1

HCID 68965163ethyl 5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}nicotinateYield 21.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5,6-dichloronicotinic acid (356 mg), iodoethane (318 mg) and potassium carbonate (308 mg) in N,N-dimethylformamide (3 mL) was heated at eighty degree for fourteen hours. The mixture was allowed to cool to ambient temperature and to this was added (3R)-1-(cyclohexylmethyl)-3-piperidinamine dihydrochloride (549 mg) and potassium carbonate (898 mg) and heated at eighty degree for thirtyeight hours. The mixture was allowed to cool to ambient temperature and was added water. The mixture was extracted with ethyl acetate (100 mL) and aqueous phase was separated. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was filtered and evaporated in vacuo to give an amorphous solid. The crude solid was purified by a flash chromatography eluting with 3% methanol-chloroform (v/v) to give ethyl 5-chloro-6-{[(3R)-1-(cyclohexylmethyl)-3-piperidinyl]amino}nicotinate (154 mg) as a pale yellow amorphous solid.

Workup

  1. temperaturewas heated at eighty degree for fourteen hours
  2. temperatureheated at eighty degree for thirtyeight hours
  3. temperatureto cool to ambient temperature
  4. extractionThe mixture was extracted with ethyl acetate (100 mL) and aqueous phase
  5. customwas separated
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationThe solvent was filtered
  9. customevaporated in vacuo
  10. customto give an amorphous solid
  11. customThe crude solid was purified by a flash chromatography
  12. washeluting with 3% methanol-chloroform (v/v)

Sources & evidence

ORD record
ord-ff31a2b2b1b2433794f0f6b1e2736e2c
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

Loading…